Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers Summary Oropharyngeal cancer and anal cancer have been recently highlighted in the annual `Report to the Nation on the Status of Cancer' as ebing the two cancers in the US that are increasing among both men and women. Our proposal focuses on these two cancers. Our pilot data from the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort indicate that circulating HPV16 E6 antibodies are present over 10 years before diagnosis in a large proportion of people who develop oropharyngeal cancer (35%), whilst being rare among controls (0.6%). We have subsequently identified HPV16 E6 antibodies in 29% of anal cancers and, again, being extremely rare among a separate group of controls (0.6%). These results are noteworthy as they indicate that a HPV-driven neoplastic process is present many years prior to diagnosis for both of these cancers, and raises the possibility that HPV16 E6 antibodies can be used as a highly specific biomarker to predict cancer onset. We have already established a cohort consortium in order to evaluate the sensitivity, specificity, and true latent period of HPV16 E6 antibody response before diagnosis, as well as survival outcome among all head and neck cancers for those who test positive. By bringing together 10 prospective cohorts from the US and Northern Europe, two populations where HPV infection now being recognized as the predominant cause of oropharynx cancer, we plan to identify 252 new oropharyngeal cancers and 180 anal cancer cases with pre-diagnostic blood samples available for analysis. We will also collect tumor tissue from 100 oropharynx cancer cases and 50 anal cases to evaluate the correlation between serology and tumor biomarkers of HPV infection.